# US 12,180,196 B2 · Azetidine-substituted pyridine and pyrazine compounds as inhibitors of cannabinoid receptor 2

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- Number: US 12,180,196 B2
- Document ID: US12180196B2
- Status: Granted
- Kind: B2
- Application number: 17/125,648
- Filed: 2020-12-17
- Published: 2021-05-06
- Granted: 2024-12-31
- Earliest claimed: 2018-06-27
- Assignees: Hoffmann-La Roche Inc.; Eidgenoessische Technische Hochschule Zuerich
- Applicants: Hoffmann-La Roche Inc.; Eidgenoessische Technische Hochschule Zuerich
- Inventors: Simon M. Ametamey; Luca Gobbi; Uwe Grether; Julian Kretz
- Web page: https://patentgrep.com/patent/US12180196B2

## CPC

- C07D 405/14: containing three or more hetero rings
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 31/4427: containing further heterocyclic ring systems
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 23/02: Local anaesthetics
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to a compound of formula (I) wherein A1 and R1-R4 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

## Claims

### Claim 1

A compound of formula (I)
wherein
A is —CH— or nitrogen;
R1 is haloalkoxyazetidinyl, halosulfonylazetidinyl, 3-fluoro-3,3-dideuteriopropyloxyazetidinyl, 2-fluoro-2,2-dideuterio-ethyloxyazetidinyl, fluorodideuteriomethoxyazetidinyl, 2-fluoro-2,2-dideuterioethylazetidinyl or fluorodideuteriomethylazetidinyl;
R2 and R3 are both alkyl at the same time; or
R2 and R3, together with the carbon atom to which they are attached, form oxetanyl; and
R4 is alkoxycarbonyl or aminocarbonylalkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein A is —CH—.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1 is haloalkoxyazetidinyl.

### Claim 4 (depends on 3)

The compound of claim 3, wherein R1 is fluoroethoxyazetidinyl.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R2 and R3 are both ethyl at the same time.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R4 is alkoxycarbonyl.

### Claim 7 (depends on 6)

The compound of claim 6, wherein R4 is ethoxycarbonyl.

### Claim 8 (depends on 1)

The compound of claim 1 selected from the group consisting of:
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(3-fluoropropoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(2-fluoroethoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(fluoromethoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
N-[3-(2-amino-2-oxoethyl)oxetan-3-yl]-6-(cyclopropylmethoxy)-5-[3-(2-fluoroethoxy)azetidin-1-yl]pyridine-2-carboxamide;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(fluorosulfonyl)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(fluorosulfonyl)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-(3-{[3-fluoro(3,3-dideuterio)propyl]oxy}azetidin-1-yl)pyridine-2-carbonyl]amino}-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-(3-{[2-fluoro(2,2-dideuterio)ethyl]oxy}azetidin-1-yl)pyridine-2-carbonyl]amino}-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-(3-{[fluoro(dideuterio)methyl]oxy}azetidin-1-yl)pyridine-2-carbonyl]amino}-2-ethylbutanoate;
N-[3-(2-amino-2-oxoethyl)oxetan-3-yl]-6-(cyclopropylmethoxy)-5-(3-{[2-fluoro(2,2-dideuterio)ethyl]oxy}azetidin-1-yl)pyridine-2-carboxamide;
ethyl 2-{[6-(cyclopropylmethoxy)-5-{3-[2-fluoro(2,2-dideuterio)ethyl]azetidin-1-yl}pyridine-2-carbonyl]amino}-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-{3-[fluoro(dideuterio)methyl]azetidin-1-yl}pyridine-2-carbonyl]amino}-2-ethylbutanoate; and
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(2-fluoroethyl)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The compound of claim 1, wherein the compound is
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(2-fluoroethoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.